The overall goal of this research is to evaluate various chemical modification procedures for their ability to overcome many of the biological limitations of enzyme therapy such as immunogenicity, rapid clearance, poor biological stability, inadequate pH optima, and poor in vivo distribution. To accomplish this task various amino acid-N-carboxyanhydrides will be polymerized with various enzymes of interest in cancer therapy (asparaginase, carboxypeptidase G, phenylalanine ammonia lyase, and glutaminase) and the above biological properties evaluated. In addition, further preclinical evaluation of poly-D,L-alanyl-asparaginase will continue because these preparations have already shown improved immunogenic, clearance, stability, and therapeutic properties in mice. Also, the in vivo distribution of modified carboxypeptidase G will be evaluated for high dose ip MTX rescue therapy with ascites tumors.